Receptor Tyrosine Kinases: Principles and Functions in Glioma Invasion

  • Mitsutoshi NakadaEmail author
  • Daisuke Kita
  • Lei Teng
  • Ilya V. Pyko
  • Takuya Watanabe
  • Yutaka Hayashi
  • Jun-ichiro Hamada
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 1202)


Protein tyrosine kinases are enzymes that are capable of adding a phosphate group to specific tyrosines on target proteins. A receptor tyrosine kinase (RTK) is a tyrosine kinase located at the cellular membrane and is activated by binding of a ligand via its extracellular domain. Protein phosphorylation by kinases is an important mechanism for communicating signals within a cell and regulating cellular activity; furthermore, this mechanism functions as an “on” or “off” switch in many cellular functions. Ninety unique tyrosine kinase genes, including 58 RTKs, were identified in the human genome; the products of these genes regulate cellular proliferation, survival, differentiation, function, and motility. Tyrosine kinases play a critical role in the development and progression of many types of cancer, in addition to their roles as key regulators of normal cellular processes. Recent studies have revealed that RTKs such as epidermal growth factor receptor (EGFR), platelet-derived growth factor receptor (PDGFR), c-Met, Tie, Axl, discoidin domain receptor 1 (DDR1), and erythropoietin-producing human hepatocellular carcinoma (Eph) play a major role in glioma invasion. Herein, we summarize recent advances in understanding the role of RTKs in glioma pathobiology, especially the invasive phenotype, and present the perspective that RTKs are a potential target of glioma therapy.


Glioma Glioblastoma Invasion Tyrosine kinase receptor EGFR PDGFR c-Met Tie Axl DDR1 Eph TrkA Cross-talk Tyrosine kinase inhibitor Clinical trial 





Blood brain barrier


Connective tissue growth factor


Discoidin domain receptor 1


Endothelial cell


Extracellular matrix


Epidermal growth factor receptor


Erythropoietin-producing human hepatocellular carcinoma


Extracellular signal-regulated kinase


Focal adhesion kinase


Fibroblast growth factor receptor


Growth arrest–specific gene 6


Glioblastoma multiforme




Heparin-binding EGF-like growth factor


Hepatocyte growth factor


Hypoxia inducible factor


Isocitrate dehydrogenase-1


Janus kinase


Mitogen-activated protein kinase


MAPK kinase


Matrix metalloproteinase


Monoclonal antibody




Nerve growth factor


Nuclear factor-kappa B


Overall survival


Platelet derived growth factor receptor


Progression-free survival


Phosphatidylinositol 3-kinase


Protein kinase C


Phospholipase C


Phosphatase and tensin homolog deleted from chromosome 10


Protein tyrosine kinase


Receptor tyrosine kinase


Signal transducer and activator of transcription


A member of the Tyro3, Axl, and Mer family of receptor tyrosine kinase


The Cancer Genome Atlas


Transforming growth factor alpha


Tyrosine kinase inhibitor




Neurotrophic tyrosine kinase receptor type 1


Urokinase-type plasminogen activator


Vascular endothelial growth factor


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Copyright information

© Springer Nature Switzerland AG 2020

Authors and Affiliations

  • Mitsutoshi Nakada
    • 1
    Email author
  • Daisuke Kita
    • 1
  • Lei Teng
    • 2
    • 3
  • Ilya V. Pyko
    • 1
  • Takuya Watanabe
    • 1
  • Yutaka Hayashi
    • 1
  • Jun-ichiro Hamada
    • 1
  1. 1.Department of Neurosurgery, Division of Neuroscience, Graduate School of Medical ScienceKanazawa UniversityKanazawaJapan
  2. 2.Department of Neurosurgery, Division of Neuroscience, Graduate School of Medical ScienceKanazawa UniversityKanazawaJapan
  3. 3.Department of NeurosurgeryThe First Clinical College of Harbin Medical UniversityNangang districtPeople’s Republic of China

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